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Characterization of promoter elements directing Mona/Gads molecular adapter expression in T and myelomonocytic cells: involvement of the AML‐1 transcription factor
Author(s) -
Guyot B.,
Mouchiroud G.
Publication year - 2003
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0502244
Subject(s) - irf8 , transcription factor , biology , jurkat cells , myeloid , microbiology and biotechnology , runx1 , myeloid leukemia , gata2 , cell culture , promoter , t cell , gene , gene expression , cancer research , genetics , immune system
Monocytic adaptor (Mona, also called Gads) is a molecular adaptor implicated in T cell activation and macrophage differentiation. The objective of this study was to identify elements regulating specific expression of Mona/Gads in human T cell and myelomonocytic cell lines. We first confirmed that the −2000 to +150 genomic region relative to the Mona gene transcription start site is sufficient to direct specific reporter gene expression in T cell lines, Jurkat, and MOLT‐4 and in the immature myeloid cell lines, KG1a and RC2A. Deletion analysis and electrophoresis mobility shift assay identified several cis regulatory elements: overlapping initiator sequences, one interferon response factor‐2 (IRF‐2)‐binding site at position −154, one GC box recognized by Sp1 and Sp3 at position −52, and two acute myeloid leukemia (AML)‐1 binding sites at positions −70 and −13. Site‐directed mutagenesis experiments indicated a key role of AML‐1 for driving Mona expression in T cells and myeloid cells, and involvement of Sp1/Sp3 and IRF‐2 transcription factors to modulate Mona expression in a cell‐specific manner.